No description available.

In this dissertation, we propose a computational approach using a resampling based permutation test as an alternative to MCP-Mod (a hybrid framework integrating the multiple comparison procedure and the modeling technique) and gMCP-Mod (generalized MCP-Mod) [11], [29] in the step of identifying significant dose-response signals via model selection. We name our proposed approach RMCP-Mod or gRMCP-Mod correspondingly. The RMCP-Mod/gRMCP-Mod transforms the drug dose comparisons into a dose-response model selection issue via multiple hypotheses testing, an area where not much extended researches have been done, and solve it using resampling based multiple testing procedures [38]. The proposed approach avoids the inclusion of the prior dose-response knowledge known as "guesstimates" used in the model selection step of the MCP-Mod/gMCP-Mod framework, and therefore reduces the uncertainty in the significant model identification. When a new drug is being developed to treat patients with a specified disease, one of the key steps is to discover an optimal drug dose or doses that would produce the desired clinical effect with an acceptable level of toxicity. In order to nd such a dose or doses (different doses may be able to produce the same or better clinical effect with similar acceptable toxicity), the underlying dose-response signals need to be identified and thoroughly examined through statistical analyses. A dose-response signal refers to the fact that a drug has different clinical effects at many quantitative dose levels. Statistically speaking, the dose-response signal is a numeric relationship curve (shape) between drug doses and the clinical effects in quantitative measures. It's often been a challenge to nd correct and accurate efficacy and/or safety dose-response signals that would best describe the dose-effect relationship in the drug development process via conventional statistical methods because the conventional methods tend to either focus on a fixed, small number of quantitative dosages or evaluate multiple pre-denied dose-response models without Type I error control. In searching for more efficient methods, a framework of combining both multiple comparisons procedure (MCP) and model-based (Mod) techniques acronymed MCP-Mod was developed by F. Bretz, J. C. Pinheiro, and M. Branson [11] to handle normally distributed, homoscedastic dose response observations. Subsequently, a generalized version of the MCP- Mod named gMCP-Mod which can additionally deal with binary, counts, or time-to-event dose-response data as well as repeated measurements over time was developed by J. C. Pinheiro, B. Bornkamp, E. Glimm and F. Bretz [29]. The MCP-Mod/gMCP-Mod uses the guesstimates" in the MCP step to pre-specify parameters of the candidate models; however, in situations where the prior knowledge of the dose-response information is difficult to obtain, the uncertainties could be introduced into the model selection process, impacting on the correctness of the model identification. Throughout the evaluation of its application to the hypothetical and real study examples as well as simulation comparisons to the MCP-Mod/gMCP-Mod, our proposed approach, RMCP-Mod/gRMCP-Mod seems a viable method that can be used in the practice with some further improvements and researches that are still needed in applications to broader dose-response data types. / Statistics

Human rotavirus (HRV) and human norovirus (HuNoV) are the most common causative agents of acute gastroenteritis- (AGE) related morbidity and mortality around the world. Gnotobiotic (Gn) pigs are the ideal large-animal model that allows for accurate, and precise, preclinical evaluation of vaccine efficacy. Similarities in gastrointestinal anatomy, physiology, and immune system allows for direct translation of results from Gn pigs to humans. Commercially available HRV vaccines perform significantly poorer in low- and middle- income countries as compared with developed countries. Non-replicating rotavirus vaccines (NRRVs) have been proposed as a viable solution to the problems facing currently available live-, attenuated oral vaccines and evaluation of a NRRV was the first research project in this dissertation. Three doses of a novel parenterally administered nanoparticle-based RV vaccine, P24-VP8*, adjuvanted with Al(OH)3 adjuvant, was able to prime VP8*-specific mucosal and systemic T cell responses (IFN-γ producing CD4+ and CD8+ T cells), and to induce strong systemic B cell responses (IgA, IgG and serum neutralizing antibodies). A significant reduction in the mean diarrhea duration, fecal virus shedding titers, and significantly lower fecal cumulative consistency scores was observed among vaccinated pigs demonstrating the efficacy of the vaccine against RV infection and diarrhea. Next, we determined the median infectious dose (ID50) and median diarrhea dose (DD50) of the GII.4/2003 Cin-1 variant of HuNoV in Gn pigs to better standardize the pig model for HuNoV vaccine evaluation. Gn pigs were inoculated with 7 different doses of Cin-1 at 33-34 days of age. Pigs were monitored daily from post-inoculation day (PID) 1 to 7, for fecal virus shedding and fecal consistency to evaluate the virus infectiousness and associated diarrhea. The Log10 ID50 and DD50 were determined based on various mathematical models to be between 3.11 to 3.76, and 3.37 to 4.87 RNA copies, respectively. The Beta-Poisson was identified to be the best-fitting statistical model for estimating both the ID50 and DD50 of Cin-1. Determining the ID50 of the challenge virus strain is crucial for identifying the true infectiousness of HuNoVs and for accurate evaluation of protective efficacies in pre-clinical studies of therapeutics, vaccines and other prophylactics using this reliable animal model. The lack of an easily reproducible cell culture model for HuNoV has significantly delayed the development of effective vaccines. There is still no HuNoV vaccine available. Currently, the vaccine development efforts are mostly based on genetically engineered virus-like particles (VLPs) comprised of the major HuNoV capsid protein VP1. We tested the immunogenicity of a novel tetravalent VLP vaccine containing 4 major HuNoV genotypes (GI.1, GII.3, GII.4 and GII.17) using Gn pigs and evaluated its protective efficacy when challenged with GII.4 Cin-1 HuNoV. Three doses of the VLP vaccine with Al(OH)3 adjuvant administered to Gn pigs intramuscularly (IM), induced high levels of VLP-specific serum IgA and IgG antibody and hemagglutination inhibition antibody responses in the vaccinated pigs. VLP-specific IFN-γ producing CD4+ and CD8+ T cells were also elevated among vaccinated pigs at post-challenge day (PCD) 7 in the spleen and blood, but not in the ileum. However, the vaccinated pigs were not protected from infection and diarrhea when challenged with any one of the three different doses (2 x 105, 8 x 104, and 2 x 104 genome RNA copies) of Cin-1 HuNoV. These results indicated that the IM tetravalent VLP vaccine was highly immunogenic, but the presence of high levels of immune effectors induced by the vaccine were not sufficient for protecting the Gn pigs from Cin-1 challenge. Amino acid (aa) sequence analysis showed that the GII.4 Sydney 2012 strain which was included in the VLP vaccine, had 23 aa substitutions in the major receptor binding domain (P2) compared to the Cin-1, a GII.4 Farmington Hills 2002 strain. Our findings, for the first time, provided in vivo experimental evidence for the total lack of cross-genogroup, cross-genotype and cross-variant protection among HuNoV. This finding has importance implications for HuNoV vaccine development. HuNoV vaccines have to include multiple variants and have to be routinely updated in order to ensure sustained protection among the population. Together these three studies in this dissertation demonstrate the versatility of Gn pigs as a reliable large animal model for studying the pathogenesis and immunity of enteric viruses and the evaluation of immunogenicity and protective efficacy of novel enteric viral vaccines. / Doctor of Philosophy / People of all age groups are susceptible to acute gastroenteritis (AGE), a condition characterized by sudden onset of diarrhea, nausea and abdominal cramps. The two most important viral pathogens responsible for causing AGE are rotavirus (RV) and norovirus (NoV). Gnotobiotic (Gn) pigs have been valuable in helping us understand the mechanism of infection, pathogenesis, immunity and have played a key role in the expediting development of novel vaccines and therapeutics against both of these viruses. Live oral RV vaccines are available but they are not very effective in low income countries where the vaccines are needed the most. Next generation parenteral vaccines are proposed to improve the RV vaccine efficacy. Our first study showed that a nanoparticle-based intramuscular (IM) RV vaccine effectively reduced the duration and severity of human RV infection and diarrhea in Gn pigs. Secondly, we examined in detail the infectivity of HuNoV and identified accurately using different mathematical models on how much virus would be required to infect and cause diarrhea in naïve Gn pigs. This knowledge would greatly help in the accurate assessment of the efficacy of NoV vaccines. Third, we evaluated the immunogenicity and protective efficacy of a tetravalent IM NoV vaccine in Gn pigs. Although the vaccine was highly immunogenic, it did not confer any protection against infection and diarrhea upon challenge with the NoV at different doses. NoVs are so diverse that one year we might be infected with one strain and a few years later, we might be infected again with another strain, even though they belong to the same genotype, and experience the same symptoms. This is because, changes brought about due to mutation in the virus capsid protein allow the viruses to hide from neutralizing antibodies induced by previous infection or vaccination as we have revealed in this study. NoV diversity and lack of cross protection need to be taken into consideration during vaccine development. This thesis shows how Gn pigs can be used to study these components in order to further maximize our ability to understand and combat enteric viral diseases.

The purpose of this research was to study vitamin A status in grazing horses throughout the year and to evaluate the effectiveness of vitamin A and β-carotene as supplements. Vitamin A status was assessed by serum retinol concentrations (SR) and the relative dose response (RDR) which was adapted for use in the horse. The horses (45 Thoroughbred mares) were divided into three diet groups: pasture and hay only (PH); pasture, hay and vitamin A-free concentrate (PHC); and hay and vitamin A-free concentrate (HC). The mares, as well as their foals, were assessed for vitamin A status during the summer, fall and winter. After eight months, each diet group was subdivided and supplemented with either: retinyl palmitate at two times the recommended level (A), the equivalent in water dispersible β-carotene (B), or a placebo (C). Supplementation continued for 20 months during which the vitamin A status was assessed every 60 days in the mares, and at birth in the neonates. During both the depletion and the repletion phase the mares were kept on a regular breeding schedule and the reproductive rates were determined as well as the general health of the mares and their offspring. The RDR proved more sensitive at detecting changes in vitamin A status than SR, and a combination of both was used. A measurable decline in vitamin A stores was seen in the HC group within 2 months, and in PH and PHC groups during the winter. The HC group remained lower in vitamin A status throughout the study. A seasonal fluctuation of vitamin A status was observed regardless of supplementation. Supplementation with retinyl palmitate improved vitamin A status in all three diet groups, however, supplementation with β-carotene did not. Both neonates and young growing horses were lower in vitamin A status than the adult. A respiratory infection observed in the weanlings affected vitamin A status as well. Supplementation of the dam had no effect on neonatal vitamin A status. Deleterious effects on reproductive rates and health were also observed with vitamin A depletion. Supplementation of β-carotene had a negative effect on reproductive rates in this study. / Ph. D.

Doctor of Philosophy / Department of Agronomy / Kassim Al-Khatib / Mitchell R. Tuinstra / Sorghum acreage is declining throughout the United States because management options and yield have not maintained pace with maize improvements. The most extreme difference has been the absence of herbicide technology development for sorghum over the past twenty years. The objectives of this study were to evaluate the level of resistance, type of inheritance, and causal mutation of wild sorghums that are resistant to either acetyl-coenzyme A carboxylase (ACCase)-inhibiting herbicides or acetohydroxyacid synthase (AHAS)-inhibiting herbicides. ACCase-inhibiting herbicides used in this study were aryloxyphenoxypropionate (APP) family members fluazifop-P and quizalofop-P along with cyclohexanedione (CHD) family members clethodim and sethoxydim. The level of resistance was very high for APP herbicides but low to nonexistent to CHD herbicides. With genetic resistance to APP herbicides, the resistance factors, the ratio of resistance to susceptible, were greater than 54 to 64 for homozygous individuals and greater than 9 to 20 for heterozygous individuals. Resistance to CHD herbicides was very low with resistance factors ranging from one to about five. Genetic segregation studies indicate a single gene is the cause of resistance to APP herbicides. Sequencing identified a single mutation that results in cysteine replacing tryptophan (Trp-2027-Cys). Trp-2027-Cys has previously been reported to provide resistance to APP but not CHD herbicides. The other wild sorghum evaluated in this study was resistant to AHAS-inhibiting herbicides including imidazolinone (IM) family member, imazapyr, and sulfonylurea (SU) family member, nicosulfuron. Resistance factors in this genotype were very high, greater than 770 for the IM herbicide and greater than 500 for the SU herbicide, for both herbicide chemical families. Genetic segregation studies demonstrate that resistance was controlled by one major locus and two modifier loci. DNA sequencing of the AHAS gene identified two mutations, Val-560-Ile and Trp-574-Leu. Val-560-Ile is of unknown importance, but valine and isoleucine are similar and residue 560 is not conserved. Trp-574 is a conserved residue and Leu-574 is a known mutation that provides strong cross resistance to IM and SU herbicides. The results of these studies suggest that these sources of APP, SU, and IM resistance may provide useful herbicide resistance traits for use in sorghum.

Outputs of dose–response assessments can be used as benchmarks that help to identify the need for risk management measures to reduce population health risks associated with exposure to chemicals. Various approaches can be used to facilitate the incorporation of chemical- or scenario-specific data into dose–response analyses, as a means of replacing or influencing default assumptions and extrapolations. The goal of the first part of this thesis was to examine the evolution of approaches to the incorporation of chemical- and scenario-specific data in dose–response assessments in regulatory settings, and identify contextual factors that serve as barriers and facilitators to the use of approaches. A main focus of the investigation was on physiological modelling, which is the most commonly-used category of approaches enabling extrapolations that depart from default assumptions. Evaluations of the dose–response applications of physiological modelling in the peer-reviewed scientific literature and in regulatory reports were conducted. Similarities between the scientific literature databases and regulatory reports were observed with respect to the evolution of physiological modelling in dose–response assessments, notably related to the timing, quantity, and annual frequency of publications. These similarities indicate that a factor in the low dose–response application of physiological modelling, relative to the overall production of physiological models, is an absence of data. However, variability in adoption of physiological modelling in regulatory dose–response assessments was observed among—and even within—organizations faced with the same data, indicating that other factors influence regulatory uptake of physiological modelling. Analysis of a survey indicated that factors acting as barriers or facilitators to regulatory risk assessors’ incorporation of increasingly data-informed approaches originated in both external and internal contexts. The external context was composed of the regulatory environment, domestic and international alignment, availability of external expertise, background of peer reviewers and stakeholders, availability and accessibility of software and tools, and chemical-dependent factors. The internal context was influenced by problem formulation, time and financial resources, organizational and management support, and training. A conceptual framework demonstrating how these factors impact a risk assessor’s ability to incorporate chemical- and scenario-specific data in dose–response analysis was developed, and subsequently used to provide recommendations on actions that could be taken to increase regulatory adoption of increasingly data-informed approaches. The second part of the thesis focused on the development of a knowledge translation tool designed to assist risk managers in the evaluation of dose–response analyses. The tool was focused on occupational exposure limits (OELs), and provides a guide to occupational hygienists in evaluating the relevance and reliability of individual OELs. When occupational hygienists are faced with multiple varying OELs for a chemical of interest, these evaluations can support the selection of the most appropriate OEL for a given situation. The usefulness of the tool was demonstrated for the selection of OELs for an OEL-rich compound (n-hexane), an OEL-poor compound (methamphetamine), and one additional compound (manganese). Such a tool can improve occupational hygienists’ understanding of the basis of OELs and the levels of protection afforded by each, which can contribute to more informed risk management decisions.

Doctor of Philosophy / Department of Agronomy / Johanna A. Dille / Challenges in weed management include occurrence of multiple weed species in the field, variable emergence among weed species, different spatial distribution and weed densities, which leads to the persistence of weed patches. The overall objective of this research was to understand the interaction of weed emergence, weed density, herbicide choice, and herbicide rate in soybean. Specific objectives were 1) to characterize the seedbank and emergence patterns of shattercane (Sorghum bicolor L.), prickly sida (Sida spinosa L.), and ivyleaf morningglory (Ipomoea hederacea Jacq.) including initial, peak, end, and duration of emergence in response to crop and herbicide treatments in soybean, and 2) to evaluate large crabgrass (Digitaria sanguinalis L.), shattercane, Palmer amaranth (Amaranthus palmeri S.), and velvetleaf (Abutilon theophrasti Medik.) mortality and dry weight reduction in response to herbicide rates across varying weed densities as well as to determine the influence of velvetleaf growth stage and density on herbicide efficacy. In the emergence study of 2006 to 2008, four treatments were nocrop, no-residual herbicide, half-rate of residual herbicide and full-rate of residual herbicide. Reduction in weed emergence was observed over the years in the same species patch. Species emerged in mid-May in both years, coinciding with soybean planting. Extended emergence was observed for shattercane when moisture was low and temperature high, while for prickly sida and ivyleaf morningglory, extended emergence was observed when moisture was high and temperature low. Applying residual herbicide decreased weed emergence. Herbicide choice was the whole plot, herbicide rates were subplots and weed densities were sub-subplots in field experiments conducted in 2006 and 2007. Shattercane was more susceptible to both glyphosate and clethodim than large crabgrass. Increasing large crabgrass density reduced percent mortality with clethodim, while with glyphosate, density did not affect both species mortality. Shattercane dry weight was reduced to 0 g per plot with 0.1X labeled rate of clethodim or glyphosate while 0.5X of the labeled rate reduced dry weight of large crabgrass to 0 g per plot. For broadleaf weeds, higher percent mortality was observed with glyphosate than with lactofen at high densities. Palmer amaranth was more susceptible than velvetleaf. Velvetleaf response was density dependent, such that increasing density did not increase dry weight. Velvetleaf growth stage was of importance, as stage affected herbicide efficacy, with higher mortality achieved at the two-leaf stage than the four- and six-leaf stages. For glyphosate, 0.125X of labeled rate on velvetleaf density of 5 seedlings per pot achieved more than 90% mortality when applied at the two-leaf stage, but dropped to 60 and 50% mortality when applied at the four- and six-leaf stage, respectively. The trend was the same for velvetleaf at a density of 30 seedlings per pot, which had 80, 60, and 55% mortality for the two-, four-, and six-leaf stages, respectively. Weed managers and farmers have the opportunity to better select herbicide choice and rate based on weed species, weed emergence patterns, and weed density.

This thesis proposes some new model independent or nonparametric methods for estimating the dose-response curve and the effective dosage curve in the context of bioassay. The research problem is also of importance in environmental risk assessment and other areas of health sciences. It is shown in the thesis that our new nonparametric methods while bearing optimal asymptotic properties also exhibit strong finite sample performance. Although our specific emphasis is on bioassay and environmental risk assessment, the methodology developed in this dissertation applies broadly to general order restricted inference.

A colina é um nutriente essencial nas dietas de frangos de corte. Os valores de exigências nutricionais são variáveis e foram estabelecidos há muitos anos. Assim, o objetivou-se com este trabalho reavaliar as respostas de frangos de corte de alto potencial genético de 1 a 7, 1 a 14 e 1 a 21 dias de idade como também modelar as respostas por diferentes funções matemáticas. Foram conduzidos dois experimentos sob dois níveis de metionina na dieta, tendo como base o método dose-resposta. Para os ensaios, foram utilizados 2.160 pintos de corte machos da linhagem Cobb 500 (1.080 em cada experimento), distribuídos em um delineamento inteiramente casualizado, com seis tratamentos, seis repetições e 30 aves por unidade experimental. Os tratamentos consistiram em rações com níveis de 390, 715, 1.040, 1.365, 1.690 e 2.015 mg/kg de colina. As rações experimentais foram formuladas utilizando-se a técnica da suplementação. Foi formulada uma ração basal à base de milho, farelo de soja, concentrado proteico de soja, açúcar e amido contendo 390 mg/kg de colina total e 0,596% de metionina digestível. O cloreto de colina (62,5%) comercial foi suplementado para obter os demais níveis. O segundo experimento consistiu nos mesmos tratamentos do primeiro, porém com atendimento de 0,440% da metionina digestível. As variáveis mensuradas em ambos os ensaios foram: consumo de ração, consumo de colina, conversão alimentar e ganho de peso. Para modelar as respostas considerou-se o consumo de colina como variável independente e ganho de peso como variável dependente. As respostas foram modeladas por cinco modelos matemáticos: broken line, broken line com ascendência quadrática, cinética de saturação, logístico e monomolecular e o melhor modelo foi selecionado pelo critério de Akaike. As análises estatísticas foram realizadas com auxílio do programa computacional SAS® utilizando o procedimento PROC GLM para análise das pressuposições e análise de variância e PROC NLIN para o ajuste dos modelos. Os modelos que melhor se ajustaram foram: Broken line com ascendência quadrática (1,26 mg/g de GP ensaio 1) e Logístico (1,26 mg/g de GP ensaio 2) para o período de 1 a 7 dias. No período de 1 a 14 dias os modelos selecionados para o experimento com metionina normal e reduzida foram Logístico (1,16 mg/g de GP) e Broken line com ascendência quadrática (1,28 mg/g de GP), respectivamente. Já para o período de 1 a 21 foram o cinética de saturação, estimando uma exigência de 1,35 mg/g de GP para o experimento com metionina normal, e Broken line com ascendência quadrática estimando uma exigência de 1,21 mg de colina/g de GP para o experimento com metionina reduzida. / Choline is an essential nutrient in the diets of chicks. Supplementation levels in feeds is variable and requirements have been established many years ago. Thus, the objective of this study was to reassess the responses of high genetic potential chicks from 1-7, 1-14 and 1 to 21 days as well as modeling the responses of different mathematical functions. Two trials were conducted using two dietary levels of methionine, based on the dose-response method. For the trials were used 2,160 Cobb 500 male broiler chicks (1,080 birds in each experiment), distributed in a completely randomized design with six treatments and six replicates and 30 birds per experimental unit. The treatments consisted of diets with levels of 390, 715, 1,040, 1,365, 1,690 and 2,015 mg/kg of choline. The diets were formulated using the supplementation method. The basal diet was formulated based on corn, soybean meal, soy protein concentrate, sugar and starch, and contained 390 mg/kg of choline and 0.596% of digestible methionine. Commercial choline chloride (62.5%) was supplemented to obtain the other levels. The second trial consisted of the same treatments of the first, but with 0.440% of digestible methionine. The variables measured in both trials were: feed intake (FI), intake of choline (IC), feed conversion (FC) and weight gain (WG). To model the responses, the variables used were the intake of choline as an independent variable and weight gain as the dependent variable. The responses were modeled by five mathematical models: broken line (ascending linear and quadratic segments), saturation kinetic, 4-parameter logistics and monomolecular models and the best model was selected by Akaike information criterion. Statistical analyzes were performed using the computer program SAS® using PROC GLM for analysis of the assumptions and analysis of variance and PROC NLIN to fit the models. The models that best fit were: broken line quadratic segments (1.26 mg/g of WG - trial 1) and Logistics (1.26 mg/g of WG - trial 2) for the period 1-7 days. In the period 1-14 days, the models selected for the experiment with normal and deficient methionine were Logistic (1.16 mg/g WG) and broken line quadratic segments (1.28 mg/g WG), respectively. For the period 1-21days, the models were the saturation kinetics, estimating a requirement of 1.35 mg/g of WG for the experiment with normal methionine, and broken line quadratic segments estimating a requirement of 1.21 mg choline/g of WG for the experiment with deficient methionine.

Recentemente, tem sido constatadas falhas no controle da planta daninha capim-branco (Chloris polydactyla) pelo herbicida glyphosate em áreas de culturas anuais e perenes no Brasil. Suspeita-se que estas falhas sejam decorrentes da seleção de populações resistentes desta planta daninha ao glyphosate. No entanto, até o momento, poucos relatos estão disponíveis na literatura caracterizando estas falhas. Esta pesquisa teve como objetivo a caracterização dos níveis de suscetibilidade de populações que apresentaram falha de controle, assim como estudar seus mecanismos de resistência. Também foi objetivo do trabalho analisar comparativamente o crescimento das populações suscetíveis e as supostamente resistentes ao glyphosate e avaliar a eficácia de herbicidas considerados alternativos ao glyphosate. Na primeira etapa, foram estudadas 87 populações do capim-branco vinda de diferentes regiões do Brasil, das quais duas sobreviveram ao experimento designado \"screening\". Esses dois biótipos, 59 e 69, juntamente com outras 15 populações suscetíveis, foram submetidos a experimentos de dose-resposta para a caracterização de suas suscetibilidades e determinação da dose eficiente de controle, da qual foi calculada em 705,41 g e.a. ha-1 de glyphosate. Em seguida, os biótipos supostamente resistentes foram comparados a um biótipo suscetível (34) para o cálculo do fator de resistência, que variou entre 3,92 e 7,95, confirmando a resistência dos biótipos. Não foi possível inferir claramente que existem diferenças de crescimento entre os biótipos resistente e suscetível que implicaria em custo adaptativo do biótipo resistente. No entanto, fica evidente que nas fases iniciais de crescimento, o biótipo 34S foi ou superior ou estatisticamente igual ao biótipo 69R. Não foi possível estabelecer uma relação entre diferenças de suscetibilidade entre os biótipos, portanto, a resistência do biótipo 69R ao glyphosate não alterou sua suscetibilidade aos herbicidas alternativos ao glyphosate aqui estudados. Na pós-emergência, clethodim e fenoxaprop-P-ethyl foram eficientes para controlar os biótipos 34S e 69R, enquanto que em pré-emergência, todos os herbicidas testados foram eficientes. O biótipo 69R absorveu menor quantidade de 14glyphosate em relação ao biótipo 34S em todos os tratamentos, do qual foi estatisticamente inferior àqueles contendo 14glyphosate + surfactante não-iônico (0,25%), 14glyphosate + sulfato de amônio (3kg ha-1) e 14glyphosate isolado. O tratamento que proporcionou maior absorção para ambos os biótipos foi o 14glyphosate + surfactante não-iônico. O biótipo 69R teve absorção máxima (Amax) 17% inferior ao biótipo 34S e maior retenção de 14glyphosate na folha tratada. O acúmulo de ácido chiquímico no biótipo 34S foi 2,56 vezes maior que no biótipo 69R. Mutações no gene que codificam a EPSPs dos biótipos 34S e 69R não foram observadas. Por fim, baseando-se nos dados aqui obtidos, é possível afirmar que a absorção reduzida, bem como a maior retenção do 14glyphosate nas folhas do biótipo 69R, possuem papel importante na resistência desse biótipo ao glyphosate. / It has been recently observed failures in controlling Tall windmill grass (Chloris polydactyla) by glyphosate in agricultural areas in Brazil. It is suspected that these failures are due to selection of resistant biotypes to glyphosate. However, to date, few reports are available in the literature characterizing these failures. Therefore, this study aimed to characterize the levels of susceptibility of differents populations of Chloris polydactyla, and to study the possible mechanisms of resistance to glyphosate. It was also an objective of this study to build a comparative growth analysis between populations, as well as evaluating the effectiveness of alternatives herbicides to glyphosate. In the first step, 87 populations from different regions of Brazil were studied, of which two survived the experiment called \"screening\". These two biotypes, 59 and 69, along with 15 other susceptible populations were subjected to a dose- response experiment for the characterization and determination of their susceptibility to glyphosate and a baseline herbicide sensitivity was obteined, which was calculated in 705.41 g ae ha-1 of glyphosate. Then the supposedly resistant biotypes (59R and 69R) were compared to a susceptible population (34S) for calculate the resistance factor, which ranged from 3.92 to 7.95, confirming the resistance of the biotypes. It was impossible to infer accurately that there are differences in growth between the resistant and susceptible biotypes of Tall windmill grass, which would imply in fitness penalty for the resistant biotype. However, it is evident that in the early growth stages, in most of the variables analyzed, the 34S was biotype or higher or statistically equal to biotype 69R. It was not possible to establish a statistical difference in susceptibility among biotypes, therefore the resistance of 69R biotype to glyphosate did not alter its susceptibility to alternative herbicides. At post-emergence, clethodin and fenoxaprop-P-ethyl were efficient to control biotypes 34S and 69R. On the other hand, at pre-emergence, all herbicides were efficient to control both biotypes. The biotype 69R absorbed smaller amount of 14glyphosate relative to 34S biotype in all treatments, which was statistically inferior to those containing 14glyphosate + non-ionic surfactant (0.25%), 14glyphosate + ammonium sulfate (3 kg ha-1) and 14glyphosate alone. The treatment providing greater absorption for both biotypes was 14glyphosate + non-ionic surfactant. Biotype 69R absorbed 17% less than the biotype 34S and had higher treated leaf retention. The shikimic acid accumulation assay in the biotype 34S was 2.56 times higher than in biotype 69R. Mutations in the gene encoding EPSPs were not observed. Finally, based on data obtained here, it is clear that the reduced absorption and treated leaf retention of 14glyphosate in biotype 69R, have an important role in the resistance of this biotype to glyphosate.